Cancer treatments called immune checkpoint inhibitors (ICIs) have changed how doctors treat cancer. These drugs work by helping a person’s immune system—especially their T-cells—find and attack tumors.
But while they can be very effective, they can sometimes cause rare but serious side effects, including dangerous inflammation in the heart. This condition is called ICI-myocarditis.
A new study led by researchers at the University of California, San Francisco (UCSF), and published in the journal Circulation, has found that a newer combination of ICI drugs may carry a higher risk for this heart inflammation.
The treatment combines two types of immune therapies that target proteins called LAG-3 and PD-1. This combination helps activate more T-cells to fight cancer, but it also increases the risk of damaging the heart.
The researchers first looked at a global safety database called Vigibase. They found that patients who received the LAG-3/PD-1 combination were four times more likely to develop myocarditis compared to those who received only PD-1 inhibitors.
To better understand what was happening, the team created a special mouse model that mimicked this condition. The mice developed serious heart inflammation, irregular heartbeats, and even early death. The researchers found that the hearts of these mice had large numbers of two immune cell types—macrophages and a specific group of T-cells.
A key discovery was that these harmful T-cells had a special marker on their surface, a protein called CXCR6. This marker acts like a “GPS tag” that helps guide immune cells to specific locations, like the heart.
When the researchers used an antibody to block CXCR6 in the mice, the animals did not develop severe heart inflammation or abnormal heart rhythms. They lived longer and had healthier hearts.
To see if this might also be true in people, the scientists examined data from human patients who had developed ICI-myocarditis. They found that people with this condition also had higher levels of CXCR6+ T-cells in their hearts, just like the mice. This suggests that CXCR6 could be a new target for treating or preventing this dangerous side effect.
Dr. Amir Munir, one of the study’s lead authors and a cardiologist at UCSF, said the findings help explain how T-cells are directed to the heart during treatment. More importantly, it points to CXCR6 as a possible target for future therapies.
While the study focused on ICI-related heart inflammation, Munir noted that this same group of T-cells might be involved in other types of heart problems, too.
The next big question, he said, is whether blocking CXCR6 would affect the cancer-fighting abilities of the immune system. If not, then this approach could offer a way to protect the heart without weakening the cancer treatment.
This research could lead to safer cancer treatments that still allow patients to benefit from powerful new immune therapies—while reducing the risk of serious side effects.
If you care about cancer, please read studies that artificial sweeteners are linked to higher cancer risk, and how drinking milk affects risks of heart disease and cancer.
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